1. Field of the Invention
This invention is directed to a method for the preparation of stable complexes of antitumor antibiotics of the anthracycline and anthraquinone classes with purified apo riboflavin binding protein from eggs, and the resulting products.
The anthracyclines and anthraquinones are a known family of antitumor antibiotics used widely for the palliative treatment of cancer. These antibiotics exhibit a number of undesirable chemical and biological properties. Some of the adverse chemical properties are poor water solubility and light-induced degradation. Some of the adverse biological properties are acute and chronic toxicity to the patient. In an effort to minimize these undesired properties, a large number of derivatives have been prepared, new methods for drug delivery explored, and various drug conjugates and complexes prepared. The present invention provides a new basis for the development of an optimal formulation for specific delivery, or controlled release of the antibiotic.
2. The Prior Art
The white and yolk of eggs contain abundant quantities of a riboflavin binding protein. This protein binds, with varying affinity, a large number of riboflavin derivatives and analogs. For these reasons it has been used frequently for the characterization of the flavin binding site using different spectroscopic probes. There is no known report, however, of this protein binding molecules structurally unrelated to the flavin (isoalloxazine) ring system.
Several methods for the conjugation or complexation of anthraquinone antibiotics have been described: covalent attachment to immunoglobulins and dextrans, intercalated into DNA fragments, and as a ferric ion complex. None have any significant advantage over the free drug for therapeutic administration, nor do any correspond to a specific complexation by a protein macromolecule. Although non-specific protein complexation of anthracycline antibiotics has been observed, they have been relatively unstable.